INFLUENCE OF THE COHESIVE BEHAVIOR OF SMALL PARTICLES ON THE SOLID-STATE PHOTOLYTIC DEGRADATION OF FUROSEMIDE

The effect of the cohesive behaviour of small particles on the solid-state photochemical degradation of furosemide is reported. Samples of agglomerated and recrystallised separated particles were exposed to direct sunlight for up to 240 hours, and the furosemide content measured with time. The solid-state photolytic degradation of furosemide proceeds from a nucleation period, through a growth period and eventual deceleration of the reaction. The kinetic process was best described by a power law dependence of the fraction degraded on time for the nucleation period and first order kinetics with asymptote, Prout-Tompkins equation, for the growth of the nuclei. The first order rate constants for the degradation of the agglomerated and the separated particles were 1.20 x 10(-2) hour-1 and 1.48 x 10(-2) hour-1 respectively for the nucleation period and 2.85 x 10(-2) hour-1 and 2.45 x 10(-2) hour-1 for the growth period. Although the mean particle size of the particles which made up the agglomerates was significantly smaller (2.5 mum) than the separated particles (22 mum), the separated particles degraded more than the agglomerates. The maximum, infinite, fraction degraded (alpha infinity) was 0.450 for the agglomerates and 0.660 for the separated particles. It seemed as though nucleation depended on the surface area exposed to irradiation. Agglomeration decreased the surface area available and therefore nucleation was less. Degradation during the growth period appeared to occur inside the particles and was limited by the extent of nucleation.